{"doi":"10.1016/j.celrep.2020.108317","title":"Heme Oxygenase-1 Induction by Blood-Feeding Arthropods Controls Skin Inflammation and Promotes Disease Tolerance","abstract":"Hematophagous vectors lacerate host skin and capillaries to acquire a blood meal, resulting in leakage of red blood cells (RBCs) and inflammation. Here, we show that heme oxygenase-1 (HO-1), a pleiotropic cytoprotective isoenzyme that mitigates heme-mediated tissue damage, is induced after bites of sand flies, mosquitoes, and ticks. Further, we demonstrate that erythrophagocytosis by macrophages, including a skin-residing CD163+CD91+ professional iron-recycling subpopulation, produces HO-1 after bites. Importantly, we establish that global deletion or transient inhibition of HO-1 in mice increases inflammation and pathology following Leishmania-infected sand fly bites without affecting parasite number, whereas CO, an end product of the HO-1 enzymatic reaction, suppresses skin inflammation. This indicates that HO-1 induction by blood-feeding sand flies promotes tolerance to Leishmania infection. Collectively, our data demonstrate that HO-1 induction through erythrophagocytosis is a universal mechanism that regulates skin inflammation following blood feeding by arthropods, thus promoting early-stage disease tolerance to vector-borne pathogens.","journal":"Cell Reports","year":2020,"id":68719,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":22,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":364098,"name":"Eva Iniguez","orcid":"0009-0006-9027-0523","position":1,"is_corresponding":false},{"id":271929,"name":"Tiago D. Serafim","orcid":"0000-0003-1606-559X","position":2,"is_corresponding":false},{"id":365479,"name":"Waldionê de Castro","orcid":null,"position":3,"is_corresponding":false},{"id":271920,"name":"Subir Karmakar","orcid":"0000-0002-6288-7335","position":4,"is_corresponding":false},{"id":365480,"name":"Maria M. Disotuar","orcid":null,"position":5,"is_corresponding":false},{"id":361783,"name":"Pedro Cecílio","orcid":"0000-0001-5945-5040","position":6,"is_corresponding":false},{"id":364099,"name":"Joshua R. Lacsina","orcid":"0000-0002-9956-8039","position":7,"is_corresponding":false},{"id":273143,"name":"Claudio Meneses","orcid":null,"position":8,"is_corresponding":false},{"id":105579,"name":"Bianca M. Nagata","orcid":"0000-0002-7479-0012","position":9,"is_corresponding":false},{"id":297377,"name":"Sílvia Cardoso","orcid":"0000-0003-4639-698X","position":10,"is_corresponding":false},{"id":364100,"name":"Daniel E. Sonenshine","orcid":"0000-0001-9370-918X","position":11,"is_corresponding":false},{"id":105612,"name":"Ian N. Moore","orcid":"0000-0002-0391-6466","position":12,"is_corresponding":false},{"id":364101,"name":"Valéria M. Borges","orcid":"0000-0002-2775-5409","position":13,"is_corresponding":false},{"id":271922,"name":"Ranadhir Dey","orcid":"0000-0003-0069-7867","position":14,"is_corresponding":false},{"id":297382,"name":"Miguel P. Soares","orcid":"0000-0002-9314-4833","position":15,"is_corresponding":false},{"id":271939,"name":"Hira L. Nakhasi","orcid":"0000-0003-4941-1620","position":16,"is_corresponding":false},{"id":271926,"name":"Fabiano Oliveira","orcid":"0000-0002-7924-8038","position":17,"is_corresponding":false},{"id":271936,"name":"Jesús G. Valenzuela","orcid":"0000-0002-5589-9450","position":18,"is_corresponding":false},{"id":271935,"name":"Shaden Kamhawi","orcid":"0000-0003-4304-636X","position":19,"is_corresponding":false},{"id":271928,"name":"Thiago DeSouza‐Vieira","orcid":"0000-0002-6051-8608","position":0,"is_corresponding":true}],"reference_count":73,"raw_metadata":null,"created_at":"2026-07-18T21:41:52.279368Z","pmid":"33113362","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}